Urolithiasis is a process of forming stones anywhere in urinary tract i.e. in the kidney, bladder, and/or ureters. Kidney stones are among the most common and painful disorders of the urinary tract. The term nephrolithiasis (or “renal calculus”) refers to stones located in the kidney. Kidney stones affect up to about 5% of the population, with a lifetime risk of passing a kidney stone of about 8-10%.
Urolithiasis takes place with nucleation, aggregation and retention of salts in urine wherein salts bind to the colloid matrices in the kidney and urinary tract. In this process, aggregates of tiny crystals of urinary salts are formed, named as kidney stones or renal calculi. Kidney stones or renal calculi can be classified according to the specific type of crystals they contain such as calcium oxalate, calcium phosphate, struvite, uric acid and cysteine. Some of the factors causing renal calculi are super saturation of urine with stone forming salts such as Calcium oxalate, calcium phosphate, uric acid, nutritional and environmental factors like dehydration, excess animal protein in diet, decrease in urinary pH, increase in the crystalloid level and/or fall in colloid level, change in urinary magnesium/calcium ratio, infection of the urinary tract, urinary stasis, decreased urinary output of citrate, vitamin deficiency, hyperparathyroidism and prolonged immobilization. These metabolic abnormalities are described by different terminologies such as hypercalciurea, hypocitraturia, hyperoxaluria, hyperuricosuria etc. When urine gets super saturated with stone forming salt ions such as calcium oxalate, they spontaneously join together to form solid crystals. The tiny crystals stick together forming large aggregates which get retained in the kidney and continue to grow larger. If the stones have grown to a critical size such as 5-10 mm in diameter then passage of stones through kidneys to ureters may get obstructed leading to pain and inflammation.
Physiological effect of urolithiasis depends on the size and position of the calculus. Presence of calculi can produce obstruction in the kidney leading to infection, metaplasia and parenchymal ischaemia. In case of renal calculi of one of the kidneys, compensatory hypertrophy due to over exertion can be induced in the other healthy kidney as well.
The most common complication is kidney stone recurrence. People who have passed one kidney stone have a 60-80% likelihood of having another one at some point in their life. Preventing recurrence is largely specific to the type of stone (e.g., calcium oxalate, calcium phosphate, cystine, struvite [magnesium ammonium phosphate], and uric acid stones). However, even when the stone cannot be retrieved, urine pH and 24-hour urine assessment for various parameters provide information about stone-forming factors that can guide prevention of recurrence.
Treatment for urolithiasis is decided on the basis of ultrasound scanning of the kidneys and urinary tract and analyzing the size and location of the calculi. Small sized calculi are tried for treatment with plenty of water intakes to flush out the calculi from the urinary system. This is usually supported with prescription of diuretics such as thiazides, potassium citrate etc, for increasing urination and pain killers to relieve the discomfort associated with passing out of the calculus. In USA, about 80% of renal calculi fall in this segment. Remaining 20% diagnosed with larger calculi are treated using extracorporeal shock wave lithotripsy (ESWL), percutaneous nephrolithotomy or uteroscopy. Due to the difficulty in flushing out larger sized calculi, ESWL is used to break it down so that they can be flushed out in the urine. However, ESWL is associated with side effects like moderate pain, blood in urine, bruising of back or abdomen by the sound waves, bleeding around the kidney and adjacent organs etc. Further, ESWL is not very successful in removal of large stones which are subsequently removed by surgery.
Countries of Middle East, North Africa, the Mediterranean Regions, North Western state of India, Southern State of USA and areas around the great lakes have been listed as high-risk areas and termed as the ‘stone belt’ regions of the world, where large numbers of patients suffer from renal calculi. In these countries, diagnosis and prevention of renal calculi are not taken seriously. Due to fear of surgical procedures and side effects of lithotripsy, many patients refuse to undergo these procedures. Instead they try to survive by using excessive pain killers.
Surgical procedures though effective in treatment involve high cost and lead to other side effects of urinary tract infection. Due to the limitations associated with clinical procedures to remove renal calculi, there is growing need for drugs which can help in complete removal of renal calculi. Hence there is need to develop drugs which will reduce the cost of management of the disorder and provide health to the patient by aggressive prevention of stone formation. The instant disclosure aims to address these concerns of the prior art.
Bhaskaran et al (US2008/0221173A1) discloses a pharmaceutical composition having dopaminergic activity and other related pharmaceutical activities comprising trigonelline or its derivative(s) and 4-Hydroxyisoleucine or its derivative(s), optionally along with excipients(s), and a process of preparing the composition. It also discloses a method of treating side effects caused by dopamine receptor antagonists. However this document does not suggest or teach use of said composition in managing urolithiasis and related urological disorders such as hyperoxaluria, hypocitraturia, hyperuricosuria, kidney disorders, ureterolithiasis, and obstruction in urine output, creatinine clearance and recurrence of stone formation.